A wide variety of drugs have been used in the treatment of disturbances in cardiac rhythm. The most commonly used antiarrhythmia drugs include digitalis, quinidine, procainamide, lidocaine and propranolol. Like most other drugs, toxic side effects generally accompany the use of certain of these drugs. A number of quaternary ammonium salts have been found to be effective antiarrhythmic agents with reduced side effects. Bretylium, for example, is an (o-bromobenzyl)ethyldimethylammonium salt which has been shown to be effective in the treatment of disturbances of ventricular rhythm that are not successfully abolished by conventional drugs.
While neither the causes of cardiac arrhythmias nor the modes of action of antiarrhythmic drugs are fully understood, several theories abound. It is generally accepted that differences in ionic concentrations and permeability of ionic channels across the cardiac membrane result in electrical potential differences that are somehow connected with arrhythmias. A great deal of research has accordingly been done in studying the responses of action potentials in many nerve and muscle fibers to various drugs. It is of interest to note that one of the actions of tetraethylammonium ion (a simple quaternary ammonium ion) is to specifically prolong the action potentials of many nerve and muscle fibers, see Loeb and Ewald, J. Biol. Chem., 25, 377 (1916); Schmidt, Arch. Ges. Physiol., 282, 357 (1965); and Ito et al., The American Journal of Cardiology, 41, 365 (1978).
An object of this invention is to provide a method for treating cardiac arrhythmia utilizing a certain class of tetra-alkyl quaternary ammonium salts. The compounds utilized in the method of this invention have demonstrated unexpected potency and efficacy in the prolongation of the action potential of cardiac Purkinje fibers. Pharmaceutical formulations containing such compounds are provided.